CA2412564C - Derives de purine - Google Patents

Derives de purine Download PDF

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Publication number
CA2412564C
CA2412564C CA002412564A CA2412564A CA2412564C CA 2412564 C CA2412564 C CA 2412564C CA 002412564 A CA002412564 A CA 002412564A CA 2412564 A CA2412564 A CA 2412564A CA 2412564 C CA2412564 C CA 2412564C
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CA
Canada
Prior art keywords
amino
compound
formula
alkyl
ethyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CA002412564A
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English (en)
Other versions
CA2412564A1 (fr
Inventor
Simon John Mantell
Sandra Marina Monaghan
Peter Thomas Stephenson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pfizer Inc
Original Assignee
Pfizer Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Publication of CA2412564A1 publication Critical patent/CA2412564A1/fr
Application granted granted Critical
Publication of CA2412564C publication Critical patent/CA2412564C/fr
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16Purine radicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/08Bronchodilators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10Drugs for genital or sexual disorders; Contraceptives for impotence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/04Antipruritics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/16Otologicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Reproductive Health (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Endocrinology (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Gynecology & Obstetrics (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Communicable Diseases (AREA)
  • Obesity (AREA)
  • Oncology (AREA)
  • Pregnancy & Childbirth (AREA)
  • Vascular Medicine (AREA)
  • Psychiatry (AREA)
  • Emergency Medicine (AREA)

Abstract

L'invention concerne des composés de formule (I), des sels pharmaceutiquement acceptables et des solvates correspondants. Elle concerne également des procédés de préparation d'intermédiaires utilisés dans la préparation de compositions contenant de tels composés tels que des agonistes de récepteur A2a d'adénosine, et lors des utilisations de tels composés.
CA002412564A 2000-06-27 2001-06-14 Derives de purine Expired - Fee Related CA2412564C (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB0015727.1A GB0015727D0 (en) 2000-06-27 2000-06-27 Purine derivatives
GB0015727.1 2000-06-27
PCT/IB2001/001064 WO2002000676A1 (fr) 2000-06-27 2001-06-14 Derives de purine

Publications (2)

Publication Number Publication Date
CA2412564A1 CA2412564A1 (fr) 2002-01-03
CA2412564C true CA2412564C (fr) 2007-10-02

Family

ID=9894500

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002412564A Expired - Fee Related CA2412564C (fr) 2000-06-27 2001-06-14 Derives de purine

Country Status (42)

Country Link
EP (1) EP1296996B1 (fr)
JP (1) JP2004501929A (fr)
KR (1) KR20030036248A (fr)
CN (1) CN1432020A (fr)
AP (1) AP1372A (fr)
AR (1) AR028759A1 (fr)
AT (1) ATE267836T1 (fr)
AU (1) AU2001264164A1 (fr)
BG (1) BG107171A (fr)
BR (1) BR0111912A (fr)
CA (1) CA2412564C (fr)
CZ (1) CZ20023992A3 (fr)
DE (1) DE60103537T2 (fr)
DK (1) DK1296996T3 (fr)
DO (1) DOP2001000195A (fr)
EA (1) EA200201291A1 (fr)
EC (1) ECSP024396A (fr)
EE (1) EE200200712A (fr)
ES (1) ES2220775T3 (fr)
GB (1) GB0015727D0 (fr)
GT (1) GT200100119A (fr)
HR (1) HRP20020995A2 (fr)
HU (1) HUP0301389A3 (fr)
IL (1) IL152529A0 (fr)
IS (1) IS6580A (fr)
MA (1) MA26918A1 (fr)
MX (1) MXPA03000078A (fr)
NO (1) NO20025975L (fr)
NZ (1) NZ521867A (fr)
OA (1) OA12294A (fr)
PA (1) PA8521001A1 (fr)
PE (1) PE20020213A1 (fr)
PL (1) PL361384A1 (fr)
PT (1) PT1296996E (fr)
SI (1) SI1296996T1 (fr)
SK (1) SK17332002A3 (fr)
SV (1) SV2002000507A (fr)
TN (1) TNSN01096A1 (fr)
TR (1) TR200401622T4 (fr)
UY (1) UY26797A1 (fr)
WO (1) WO2002000676A1 (fr)
ZA (1) ZA200209557B (fr)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE60215028T2 (de) 2001-08-14 2007-03-15 Eli Lilly And Co., Indianapolis Indol derivate als beta-3-adrenerge agonisten zur behandlung von typ 2 diabetes
SE0201980D0 (sv) * 2002-06-24 2002-06-24 Astrazeneca Ab Novel compounds
US6919356B2 (en) 2002-09-26 2005-07-19 Bristol Myers Squibb Company N-substituted heterocyclic amines as modulators of chemokine receptor activity
TW200519106A (en) 2003-05-02 2005-06-16 Novartis Ag Organic compounds
GB0401334D0 (en) 2004-01-21 2004-02-25 Novartis Ag Organic compounds
GB0411056D0 (en) 2004-05-18 2004-06-23 Novartis Ag Organic compounds
PE20060272A1 (es) 2004-05-24 2006-05-22 Glaxo Group Ltd (2r,3r,4s,5r,2'r,3'r,4's,5's)-2,2'-{trans-1,4-ciclohexanodiilbis-[imino(2-{[2-(1-metil-1h-imidazol-4-il)etil]amino}-9h-purin-6,9-diil)]}bis[5-(2-etil-2h-tetrazol-5-il)tetrahidro-3,4-furanodiol] como agonista a2a
EP1802316B1 (fr) * 2004-09-20 2011-11-02 Inotek Pharmaceuticals Corporation Dérivés de la purine et leurs procédés d'utilisation
GB0424284D0 (en) 2004-11-02 2004-12-01 Novartis Ag Organic compounds
GB0426164D0 (en) 2004-11-29 2004-12-29 Novartis Ag Organic compounds
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
GB0514809D0 (en) 2005-07-19 2005-08-24 Glaxo Group Ltd Compounds
EP2532679B1 (fr) 2005-10-21 2017-04-12 Novartis AG Anticorps humains dirigés contre l'IL -13 et utilisations thérapeutiques
GB0601951D0 (en) 2006-01-31 2006-03-15 Novartis Ag Organic compounds
MY146645A (en) * 2006-04-21 2012-09-14 Novartis Ag Purine derivatives for use as adenosin a2a receptor agonists
US7589076B2 (en) * 2006-05-18 2009-09-15 Pgx Health, Llc Substituted aryl piperidinylalkynyladenosines as A2AR agonists
CA2664378A1 (fr) 2006-09-29 2008-04-03 Novartis Ag Pyrazolopyrimidines utilisees comme inhibiteurs des lipides kinases pl3k
CN101522682A (zh) 2006-10-30 2009-09-02 诺瓦提斯公司 作为抗炎剂的杂环化合物
US7897737B2 (en) 2006-12-05 2011-03-01 Lasergen, Inc. 3′-OH unblocked, nucleotides and nucleosides, base modified with photocleavable, terminating groups and methods for their use in DNA sequencing
PL2231642T3 (pl) 2008-01-11 2014-04-30 Novartis Ag Pirymidyny jako inhibitory kinazy
EP2307565B1 (fr) * 2008-06-11 2017-11-29 Lasergen, Inc. Nucléosides et nucléotides reversibles marqués et leur utilisation dans la réaction de séquençage de l'adn
WO2010088335A1 (fr) 2009-01-29 2010-08-05 Novartis Ag Benzimidazoles substitués destinés au traitement d'astrocytomes
US8389526B2 (en) 2009-08-07 2013-03-05 Novartis Ag 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives
BR112012003262A8 (pt) 2009-08-12 2016-05-17 Novartis Ag compostos de hidrazona heterocíclica e seus usos para tratar câncer e inflamação
BR112012003709B1 (pt) 2009-08-17 2021-05-18 Intellikine Llc compostos heterocíclicos e usos dos mesmos
WO2012034095A1 (fr) 2010-09-09 2012-03-15 Irm Llc Composés et compositions comme inhibiteurs de trk
US8637516B2 (en) 2010-09-09 2014-01-28 Irm Llc Compounds and compositions as TRK inhibitors
WO2012107500A1 (fr) 2011-02-10 2012-08-16 Novartis Ag Composés de [1, 2, 4] triazolo [4, 3 -b] pyridazine en tant qu'inhibiteurs de la tyrosine kinase c-met
JP5808826B2 (ja) 2011-02-23 2015-11-10 インテリカイン, エルエルシー 複素環化合物およびその使用
BR112013021638A2 (pt) 2011-02-25 2016-08-02 Irm Llc "compostos inibidores de trk, seu uso e composições que os compreendem"
WO2013038362A1 (fr) 2011-09-15 2013-03-21 Novartis Ag 3-(quinolin-6-ylthio)-[1,2,4]triazolo[4,3-a]pyradines substituées en position 6 à activité tyrosine kinase
US9174994B2 (en) 2011-11-23 2015-11-03 Intellikine, Llc Enhanced treatment regimens using mTor inhibitors
CN104245701A (zh) 2012-04-03 2014-12-24 诺华有限公司 有酪氨酸激酶抑制剂的组合产品和其应用
EP2968340A4 (fr) 2013-03-15 2016-08-10 Intellikine Llc Combinaison d'inhibiteurs de kinase et ses utilisations
WO2015084804A1 (fr) 2013-12-03 2015-06-11 Novartis Ag Combinaison d'un inhibiteur de mdm2 et d'un inhibiteur de braf, et leur utilisation
WO2016011658A1 (fr) 2014-07-25 2016-01-28 Novartis Ag Polythérapie
JP6526789B2 (ja) 2014-07-31 2019-06-05 ノバルティス アーゲー 組み合わせ療法
TW202140550A (zh) 2020-01-29 2021-11-01 瑞士商諾華公司 使用抗tslp抗體治療炎性或阻塞性氣道疾病之方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU8276187A (en) * 1986-10-31 1988-05-25 Warner-Lambert Company Selected n6-substituted adenosines having selective a2 binding activity
IL107101A0 (en) * 1992-09-30 1993-12-28 Merrell Dow Pharma 2-substituted adenosines with a-2 receptor affinity
GB9723590D0 (en) * 1997-11-08 1998-01-07 Glaxo Group Ltd Chemical compounds
AU2108299A (en) * 1998-01-08 1999-07-26 University Of Virginia Patent Foundation A2A adenosine receptor agonists
DE69932173T2 (de) * 1998-10-16 2007-06-06 Pfizer Inc. Adeninderivate
GB9913932D0 (en) * 1999-06-15 1999-08-18 Pfizer Ltd Purine derivatives
GB9924363D0 (en) * 1999-10-14 1999-12-15 Pfizer Central Res Purine derivatives
GB9924361D0 (en) * 1999-10-14 1999-12-15 Pfizer Ltd Purine derivatives

Also Published As

Publication number Publication date
EP1296996B1 (fr) 2004-05-26
NO20025975D0 (no) 2002-12-12
PA8521001A1 (es) 2002-04-25
UY26797A1 (es) 2002-01-31
MA26918A1 (fr) 2004-12-20
OA12294A (en) 2003-11-14
DE60103537D1 (de) 2004-07-01
PE20020213A1 (es) 2002-03-19
HUP0301389A3 (en) 2005-02-28
CZ20023992A3 (cs) 2003-12-17
ECSP024396A (es) 2003-02-06
AR028759A1 (es) 2003-05-21
HUP0301389A2 (hu) 2003-08-28
DE60103537T2 (de) 2005-07-07
MXPA03000078A (es) 2003-08-19
SK17332002A3 (sk) 2004-03-02
SI1296996T1 (en) 2004-10-31
CN1432020A (zh) 2003-07-23
WO2002000676A1 (fr) 2002-01-03
GT200100119A (es) 2002-01-31
BR0111912A (pt) 2003-05-13
ZA200209557B (en) 2003-12-02
NZ521867A (en) 2004-04-30
NO20025975L (no) 2002-12-12
PT1296996E (pt) 2004-08-31
JP2004501929A (ja) 2004-01-22
IS6580A (is) 2002-10-10
TR200401622T4 (tr) 2004-08-23
GB0015727D0 (en) 2000-08-16
DOP2001000195A (es) 2002-05-15
AU2001264164A1 (en) 2002-01-08
KR20030036248A (ko) 2003-05-09
ATE267836T1 (de) 2004-06-15
AP1372A (en) 2005-02-21
EE200200712A (et) 2004-06-15
HRP20020995A2 (en) 2005-02-28
EP1296996A1 (fr) 2003-04-02
EA200201291A1 (ru) 2003-04-24
CA2412564A1 (fr) 2002-01-03
IL152529A0 (en) 2003-05-29
ES2220775T3 (es) 2004-12-16
BG107171A (en) 2003-07-31
PL361384A1 (en) 2004-10-04
SV2002000507A (es) 2002-07-03
TNSN01096A1 (fr) 2005-11-10
DK1296996T3 (da) 2004-08-16

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